Study Demonstrates Proof-of-Concept for Microneedle-Based Antimicrobial Sensing

A new study by investigators in the United Kingdom has demonstrated proof-of-concept for microneedle-based sensing of antimicrobials in humans.

As pharmacokinetic variation has resulted in advocating for improved methods of drug monitoring to facilitate individualized antimicrobial dosing. In response, the study team conducted an evaluation of real-time penicillin monitoring via microneedle-based penicillin biosensor.

The findings of the study were presented in a poster session at the European Congress for Clinical Microbiology and Infectious Diseases (ECCMID 2019).

Contagion® spoke to the presenter of the poster Timothy Rawson, MBBS, PhD, a clinical research fellow in the Department of Infectious Diseases at Imperial College of London, to learn more about the study (see video).

For the study, 10 healthy individuals were recruited as participants at Imperial College London, Clinical Research Facility. The mean participant age was 42 years and 70% of participants were male.

Prior to arriving at the facility, each participant took 5 doses of oral phenoxymethylpenicillin (500 mg, 6 hourly).

For the sixth penicillin dose, individuals had venous blood and interstitial fluid sampled via cannula and microdialysis, respectively. The investigators note that individual free blood drug levels were estimated.

The participants each wore 3 microneedle penicillin biosensors during this time in order to allow for real-time monitoring of interstitial fluid penicillin. The participants were also required to complete visual analogue scales related to the tolerability of wearing microneedle biosensors (0 = no discomfort, 10 = significant pain).

From there, the penicillin concentration data from the microneedles was filtered through locally-weighted-scatter-plot-smoothing and was then compared with free blood and microdialysis penicillin pharmacokinetics in a non-compartmental analysis with area-under-the-curve (AUC) compared.

The bias and limits of agreement were both investigated with Bland-Altman plots and the limit of detection for the microneedle biosensors was also estimated.

Results indicate that the mean length of time monitored from dose 6 was 224 (28) minutes. Additionally, the mean AUC was 1.56 (0.29) mg*h/L for free blood, 1.56 (0.85) mg*h/L for microdialysis, and 1.60 (1.04) mg*h/L for microneedle curves.

“In total, 440 time points were compared with mean (95%CI) difference between measurements -0.15 mg/L (95%CI: 0.20 to -0.11). Limit of detection for the microneedles was estimated at 0.10 mg/L,” the investigators write.

Overall, the study found that the microneedle was well-tolerated by the participants. The mean pain score for the microneedle was 0.4 (0.8) cm, compared to microdialysis insertion that scored 1.9 (3.8) cm.

According to the investigators, future research will build off of this study and look at incorporating “closed-loop control functions” to facilitate automated drug delivery.

The study, “Real-time, minimally invasive penicillin monitoring: a first-in-human evaluation of microneedle-based biosensor technology,” was presented in a late-breaking poster presentation on April 13, 2019, at ECCMID 2019 in Amsterdam, the Netherlands.